A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance.
A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance.
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DOI：
10.1186/s12864-017-4146-z
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发表时间：
2017-10-11
期刊：
影响因子：
4.4
通讯作者：
Zimic M
中科院分区：
文献类型：
--
作者：
Sheen P;Requena D;Gushiken E;Gilman RH;Antiparra R;Lucero B;Lizárraga P;Cieza B;Roncal E;Grandjean L;Pain A;McNerney R;Clark TG;Moore D;Zimic M
结核病(TB)是一个主要的全球健康问题，抗药性影响了控制这种疾病的努力。吡嗪酰胺(PZA)是一种用于一线和二线治疗方案的重要药物。然而，其完整的作用和抵抗机制仍不清楚。我们对从秘鲁无关结核病患者中分离的68株结核分枝杆菌的完整基因组进行了基因分型和测序。基于球粒分型，没有验证菌株的聚集型。我们分析了PZA抗性与非同义突变和特定基因之间的关系。我们发现在没有pncA突变的菌株中，pncA突变和与PZA耐药性显著相关的新基因。这些基因包括与金属离子运输、pH调节和免疫系统逃避相关的基因。这些结果提示了PZA耐药性的潜在替代机制，这在其他人群中尚未发现，支持PZA的抗菌活性可能作用于多个靶点。本文的在线版本(10.1186/s12864-0174146-z)包含向授权用户提供的补充材料。
Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear. We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion. These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets. The online version of this article (10.1186/s12864-017-4146-z) contains supplementary material, which is available to authorized users.
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DOI：
10.1126/science.1208813
发表时间：
2011-09-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shi W;Zhang X;Jiang X;Yuan H;Lee JS;Barry CE 3rd;Wang H;Zhang W;Zhang Y
通讯作者：
Zhang Y
影响因子：
3.7
作者：
Petrella S;Gelus-Ziental N;Maudry A;Laurans C;Boudjelloul R;Sougakoff W
通讯作者：
Sougakoff W
影响因子：
3.7
作者：
Chatterjee A;Saranath D;Bhatter P;Mistry N
通讯作者：
Mistry N
影响因子：
3.2
作者：
Sheen, Patricia;Lozano, Katherine;Zimic, Mirko
通讯作者：
Zimic, Mirko
影响因子：
3.4
作者：
Butler, Rachel E.;Cihlarova, Vera;Stewart, Graham R.
通讯作者：
Stewart, Graham R.